Genetic research sheds new light on Cerebral Palsy

When Donna Cappelli’s son was born 10 weeks premature, the doctors told her not to worry—it would just take him a bit longer to reach developmental milestones.

But as time passed, it became clear to Donna that this wasn’t the case. Milestone dates were passing by, and Julian couldn’t yet hold his head up, grasp for things, or hear well. By the time he was one year old he was diagnosed with cerebral palsy (CP).

Now 16, Julian has no control over his limbs, and has spastic muscle movements. Donna was on bed rest during her first pregnancy, but not when she was carrying Julian. She has always wondered if his disability could have been prevented.

"It would have been nice to know that it wasn’t something I did, that he was meant to be this way,” she says. “If maybe the CP is in his genes then I would know that even if I had been on bed rest, there’s nothing I could have done.”

New research is shedding light on this very issue by finding a way to help families understand why their child has CP. One out of every thousand children are born with this disability, and a recent study led by Kids Brain Health Network researcher Dr. Darcy Fehlings found evidence of a genetic link in children with hemiplegic CP—the most common form of the condition which affects only one side of the body.

The study revealed variations in genes critical to brain development and function, which could explain why a child has hemiplegic CP. Dr. Fehlings says in the future, genetic testing can give families peace of mind around a CP diagnosis.

“Families really want to try to understand why their child has developed cerebral palsy, it’s really important to them,” she says. “What the genomic information can do—depending on what the results are—is it could give you fairly specific information.”

Genetic research looking at all forms of CP

While this study looked only at hemiplegic CP - which affects 35 per cent of children with the disability - Dr. Fehlings says it would be ideal to look for genetic links in other forms of the condition as well.

“When we look at children with autism, for example, the [number of genetic variants] actually isn’t as high as what we’re finding with CP, and yet doing genomic testing [analysis of complex sets of genes and their interactions and effects on the body] is now routine for children with autism,” she says. “This helps speak to the argument that we should also consider routinely ordering genomic testing for children with cerebral palsy.”

CP is the most common motor disability in children, and Dr. Fehlings hopes that by gaining a better understanding of the genetics behind the condition, more treatment options will become available in the future.

“We know there’s a huge interest in neural repair and regenerative approaches for many other neurological conditions, so this work will definitely help to open up a line of research discovery that looks into this for cerebral palsy,” she says.

Stem cells as therapy

A promising avenue for treatment of CP supported by The Network is looking at ways in which activating stem cells could be a therapeutic option. Dr. Derek van der Kooy—professor of molecular genetics at the University of Toronto—says that by gaining a better understanding of how stem cells play a part in CP, his team is hoping to develop new forms of therapy.

“Motor and cognitive deficits are produced by a loss of neurons, and the only possibility to replace those lost neutrons is to make new cells from brain stem cells,” says Dr. van der Kooy. “A lot of rehabilitation work has focused on making the remaining cells that aren’t lost in CP work better, but our hypothesis is that constraint induced movement therapy actually works by activating stems cells to make new neurons.”

It’s likely that drugs will be the first form of new clinical treatment available, according to Dr. van der Kooy. The drug metformin—used to treat type two diabetes—has already been shown to activate brain stem cells, and is currently in clinical trials for CP. Dr. van der Kooy says drugs which stimulate stem cell development should be able to treat any form of CP—whether it originates from genetic mutations or a lack of oxygen at birth. The applications of these drugs could also span to other neurological disorders.

“In theory, we should be able to treat any disease that depends on a loss or dysfunction of normal cells by replacing those cells and activating stem cells,” he says. “That’s a testable hypothesis but it hasn’t been tested yet.”

Hope for the future

For Julian, his early years were filled with therapies that Donna hoped would halt the progression of his CP. Today, they focus on managing Julian’s symptoms and making him feel comfortable. Donna is hopeful about stem cell research, but her goal isn’t to fix Julian—in fact, she doesn’t think he’d be the person he is today if it weren’t for all the barriers he’s overcome.

“I would just like to remove pain from his life,” she says. “He has so many complex physical things that if you just took away two of them it would make things so much easier.”

For both Donna and Julian, any new CP research is exciting.

“When I hear they’ve discovered a gene variant I think, ‘oh great they’re still working on [CP]!’” she says. “As a parent, the more information we can get the better.”